The recent identification of virus neutralizing epitopes on the GP120 HIV coat protein as well as the identification of the cellular receptor for the AIDS virus itself have provided us with the opportunity to develop potentially effective vaccines against the AIDS virus. However, there are a number of problems that must be addressed before one can successfully prepare a synthetic peptide containing the neutralizing epitopes as a useful vaccine against HIV. (1) The first problem is that the peptide vaccine must be able to elicit antibodies which can recognize and bind with sufficiently high affinity for the native protein. (2) The second problem is that the peptide vaccine may not elicit antibodies against a neutralizing determinant of the virus. (3) Lastly, the vaccine must induce active immunity. We have focused on the first two problems, namely, how to prepare antibodies using a small peptide antigen that would cross react with native proteins and have the desired antigenic determinant. If one could design and synthesize conformationally constrained tertiary structural template (TST) molecules, then the dichotomy of reduction of the size of the peptide for limiting possible antigenic sites with increase in the size of the peptide for stabilizing the conformation of the peptide antigen could be resolved. This TST molecule will also be useful in a structure-function study of other biologically active molecules. In order to define the intermolecular interactions that reportedly stabilize the alpha-helical conformation of the four polypeptide chains attached to a template peptide, we synthesized a similar polypeptide reported by M. Mutter (Proteins 5:13, 1989). Determination of the peptide's solution conformation and other physical properties is currently underway.